1. Field of the Invention
The present invention relates an apparatus and method of filling a container through a valve assembly and, more particularly, to such a valve assembly and the method for the charging of a fresh media bed in the form of a slurry into a chromatography column without disassembling the column. This valve assembly, or a similar valve assembly, may also be utilized to remove slurry from the chromatography column.
2. Description of Related Art
Chromatography is a process of separating the components of a mixture of chemical substances through the percolation of fluid through a body or bed of comminuted or porous rigid material, known as media. In the process, the various component are often resolved by their selective retardation as they are transported through the bed by a moving fluid or buffer. A solution of the substances to be separated becomes the moving phase of the system passing through the interstices in the stationary or continuous phase which are finely divided particles, possibly in the form of a gel slurry.
The substances in the moving phase are poured into the top of a chromatography column filled with the finely divided material, i.e., the media, that can absorb differentially the substances to be separated. The particular material used for the media varies widely with the substances to be separated. As the solution percolates down the column the components are separated from the buffer fluid which generally is pumped back into the top of the column so as to again pass down through the bed as a carrier. The different substances as they travel down the column at different rates form bands of the different substances which are individually collected at the outlet.
A chromatography column typically comprises a hollow vertically disposed cylindrical housing including a liquid dispensing section at the upper end and through which the buffer and substances to be separated are dispensed to the media bed, and a liquid collecting section at the lower end for collecting the substances and buffer individually. The media or bed through which the buffer fluid and mixture to be separated and purified percolates is located between these sections. The liquid dispensing section and liquid collecting section may each include a respective plate and at least one, and generally both, of the plates may be connected in an assembly with an axially movable plunger-like body positioned within the housing at the respective end. After the column is charged with the bed media, the bodies may be forced relatively to each other to compress and pressurize the media bed which has been poured into the column. Alternatively, a fixed bed media may not employ a plunger-like body to compress the media bed.
The known prior art methods for packing the bed of small diameter columns used for research and development, e.g., only a few inches in diameter, are fully disclosed in Sakamoto et al. U.S. Pat. No. 5,021,162 dated Jun. 4, 1991. In the conventional liquid flow method applicable to columns of larger diameter used in production of useful products such as synthetic insulin, e.g., approximately two feet in diameter, the bed media slurry is poured into a reservoir which has been temporarily connected to the upper end of the chromatography column. The reservoir is then closed at the top and liquid is pumped under pressure through the reservoir and the column. Excess liquid floating above the bed is pumped from the reservoir and the reservoir is then removed. This leaves part of the bed over-flowing above the top of the column, and the column is closed after this excess bed media is removed. In that method, as with most of the other prior art proposals discussed in the aforesaid patent, the top of the column must be disconnected in order to charge or pack the bed and must then thereafter be reassembled.
U.S. Pat. Nos. 5,213,683 and 5,282,973 disclose one method and apparatus for installing a slurry into a column. This reference discloses the use of a moveable inlet nozzle for inserting into the column for dispensing slurry into the column. The use of this type nozzle may create an impression in a media bed at the point where the nozzle contacts a fixed bed as the nozzle is retracted out of the media bed during operation. This creates a pooling of the product supplied to the column and may result in inefficient distribution of the product through the column. Accordingly, there is a need for an improved method and apparatus for filling a chromatography column.
The present invention recognizes and addresses these needs and others.
Consequently, it is an object of the present invention to provide a slurry fill method and apparatus in which the fill nozzle is stationary.
It is another object of the present invention to provide a compressed gas to assist in the packing of a chromatography column media bed.
It is still another object of the present invention to provide a fluid cylinder to assist in the packing of a media bed of a chromatography column.
It is yet another object of the present invention to provide a piston to alter the operational status of a valve assembly.
Accordingly, the present invention provides a chromatography column having a media and a product inlet assembly positioned at the inlet of a nozzle-type assembly at the top of the column, the media and product inlet assembly preferably including a housing having a product/buffer inlet passage and a media inlet passage extending through the housing. A piston having a pressurized fluid source is preferably connected to the housing to assist in the filling, distributing, and/or packing of the media bed within the column. Additionally, the piston may control the operational status of the slurry inlet assembly. A similar, or the same, valve may be utilized to remove slurry from a chromatography column as well.